The use of antibodies as “magic bullets” to deliver toxins to cancer cells was proposed by Paul Ehrlich over a century ago, and the potential of targeted immunotherapy has since attracted the attention of generations of investigators. In 1975, with the development of the technology for producing monoclonal antibodies (MoAbs), (G. Kohler and C. Milstein, 1975, Nature, 256:495-497; see also Herzenberg and Milstein, Handbook of Experimental Immunology, ed. Weir (Blackwell Scientific, London), 1979, pp. 25.1-25.7), it seemed that successful antibody therapy was imminent. Early trials with monoclonal antibodies, however, revealed significant obstacles to their use in cancer therapy. Immune rejection of murine monoclonal antibodies, and low efficiencies were reported during initial clinical experience (Kwak et al., 1995, Clinical applications of monoclonal antibodies, In: Biologic Therapy of Cancer, Eds. V. T. DeVita, Jr., S. Hellman and S. A. Rosenberg, 2nd Ed., J. B. Lippincott Co., Philadelphia, Pa., pp. 553-565).
Ideally, antibody for cancer therapy should have a high affinity for its antigen, and an effective unconjugated antibody should work synergistically with the host's immune system effector mechanisms. Therapeutic antibodies that induce effector mechanisms such as antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytolysis (Waldman et al., 1994, Ann. Oncol, 5 Suppl. 1:13-17) have the potential to provide targeted cancer therapy that is safe and effective without the use of potentially harmful conjugates such as toxins or radionuclides.
Nearly all monoclonal antibodies recognizing antigens on human cancer cells also bind to normal human cells expressing the same antigen (Jurcic et al., 1996, Cancer Chemotherapy and Biological Response Modifiers Annual, Eds. Pinedo et al. pp. 168-188). This cross-reactivity potentially compromises therapeutic effectiveness and raises issues of toxicity, leading to the continued interest in defining antigenic targets that are unique to tumor cells. It is therefore highly desirable to have cancer-specific antigens and prepare cancer specific antibodies. The identification of unique cancer antigens enables the design of selective immunotherapy for neoplastic diseases. The capacity to utilize a determinant that is exclusively expressed by cancer cells or tumor cells, but that is not present in normal cells and tissues, insures the targeting and elimination of the neoplastic cells, while insulating the viability and function of normal cells. For general background in this regard, please see Colcher et al., 1981, Proc. Natl. Acad. Sci. 78:3199-3203.
The process that leads to the discovery of unique cancer antigens is, however, long, tedious and elaborate, and entails an exhaustive weeding out of antigens expressed on both cancer or tumor cells and normal tissues (see e.g. U.S. Pat. Nos. 4,172,124 and 4,196,265). This is because malignant cells resemble their normal cell counterparts. Cancer cells often have “low visibility” to an individual's immune surveillance system, due to the fact that the majority of cancer antigens are self-antigens or auto-antigens that are also expressed by normal cells. Frequently, the cancer antigen is identical to the normal antigen although it is expressed at higher levels or endowed with a negligible mutation insufficient for its distinction from the self-antigen.
In spite of the above-mentioned obstacles, the present invention provides new and specific monoclonal antibodies which are immunoreactive with a cancer-specific cell surface antigen and which are useful in immunotherapy, diagnostic, imaging, monitoring and screening methodologies.
The monoclonal antibody 7C8 aides in the diagnosis, prognosis, and treatment of human cancers including breast and lung cancers. The antibody is reactive to only human cancer cells but not to apparently normal human tissues.